Gliederung

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder mainly affecting the motor system. In spite of rapid advances in PD research no disease-modifying treatment is available to date, particularly treatment options for non-motor symptoms are lacking. One cause of failure might be the etiologic heterogeneity of PD. However, mitochondrial dysfunction (MD) is proven for gene associated PD (Parkin and PINK1) [1], and there is convincing evidence for a benefit of coenzyme Q10 on mitochondrial function. Thus, we suppose an increase of the effect of Q10 with increasing degree of patients’ MD.

Aim of the study: We present the design of a double-blind, randomised, placebo-controlled multi-centre phase II clinical trial to investigate the efficacy of Q10 in PD patients depending on the degree of patients’ MD.

Methods/Design: PD patients diagnosed according to UK Brain Bank criteria and with a stable PD medication over four weeks will be recruited. Four groups of patients will be investigated: carriers of two mutations in the PINK1 and Parkin gene (P++ in this trial), carriers of one mutation in the respective genes (P+), patients identified by an innovative omics-approach applying a genetic risk score who do (Omics+) or do not have (Omics-) a MD profile. Study participants will be centrally randomised to Q10 or placebo stratified by genetic profile and centre. Primary endpoint of this study will be the difference of change of motor functions assessed by the modified version of the „Unified Parkinson Rating Scale“ (MDS-UPDRS III) between Q10 and placebo group after 6 months. We hypothesize a gradient of MD between groups from P++ to Omics-, translating into a gradient of clinical benefit under Q10. Therefore, the primary analysis will be conducted using the two-sided exact trend test estimated from linear regression in the full analysis set. Sample size calculation is based on the minimal clinical difference reported for the original UPDRS and is corrected by the squared correlation between both scales [2]. About 80 PD patients will be recruited for this trial. As secondary efficacy endpoints, we will assess e.g. further motor tests, imaging endpoints (MRT/MRSI), quality of life, depression and fatigue. The course of all primary and secondary endpoints will be investigated over a period of 9 months. Safety endpoints are the number of (serious) adverse events. Furthermore, several laboratory parameters will be measured and controlled (e.g. hemogram, liver, kidney, Q10 level). Subgroup analyses and stratified analyses according to genetic profile and centre will be performed.

Discussion: The results of this study might help to elucidate one of the mechanisms in the pathophysiology of PD and could improve selection of PD patients for further trials. Furthermore, the design of this study will be useful for other researchers planning further studies.